目的 研制一种能提高水难溶性药物波棱甲素（herpetrione，HPE）口服生物利用度的新剂型——纳米混悬口腔速溶膜（nanosuspension orodispersible film，NS-ODF），并优化其处方。方法 采用高压均质法制备纳米混悬剂（NS），进一步制成口腔速溶膜（orodispersible film, ODF）。以羟丙甲纤维素（hydroxy-propyl methyl cellulose，HPMC）、低取代羟丙基纤维素（low-substituted hydroxypropyl cellulose，L-HPC）和微晶纤维素（microcrystalline cellulose，MCC）用量为考察因素，以崩解时间、5 min时累积释放度和膜复溶后的纳米粒粒径为指标，采用Box-Behnken设计试验优化HPE-NS-ODF的处方。结果 以最优处方：50 g/L HPMC、5 g/L L-HPC、1.2 g/L MCC制得的HPE-NS-ODF崩解时间为（14.19±0.61）s，5 min时药物体外释放度为（76.08±3.79）%，膜复溶后的纳米粒粒径为（289.64±5.92）nm，理论预测值与实测值偏差较小，模型具有良好的预测性。结论 采用Box-Behnken效应面法优化HPE-NS-ODF处方是有效、可行的，NS-ODF结合NS和ODF的双重优点，具有广阔的应用前景。

Objective To prepare a new dosage form—nanosuspension orodispersible film (NS-ODF) for improving the oral bioavailability of water insoluble drug herpetrione, and to optimize its formulation. Methods NS was prepared by high pressure homogenization and then transformed into ODF. The formulation of NS-ODF was optimized by Box-Behnken design-response surface method with the amounts of hydroxy-propyl methyl cellulose (HPMC), low-substituted hydroxypropyl cellulose (L-HPC), and microcrystalline cellulose (MCC) as investigation factors, and disintegration time, cumulative release of drug from the NS-ODF within 5 min, and particle size of reconstituted nanoparticles from NS-ODF as indexes. Results The NS-ODF prepared by optimal formulation (50 g/L HPMC, 5 g/L L-HPC, and 1.2 g/L MCC) could disintegrate in (14.19 ± 0.61) s and release in vitro at 5 min to (76.08 ± 3.79)%, and the particle size of reconstituted nanoparticles from NS-ODF was (289.64 ± 5.92) nm. There was a little deviation between the theoretically predicted value and the measured value. It showed that this model had a good prediction. Conclusion Using Box-Behnken design-response surface method to prepare NS-ODF is effective and feasible. NS-ODF which has both advantages of NS and oral fast dissolving film is a new dosage form with profound application prospect.

国家新药创制重大专项（2013ZX09J13109-06C）；国家教育部留学归国人员科研启动基金（20101561）；北京市自然科学基金（7122176）